There are at least five genetically distinct collagen types whose degradation may be controlled independently. The initial step of collagen degradation is performed by collagenase. We were the first to find that type IV basement membrane collagen and type V collagen is not degraded by human skin collagenase suggesting that a separate collagenase may degrade types IV and V collagen. A collagenase which preferentially degrades type IV collagen has been derived from metastatic tumor cells and from mammary epithelium. This collagenase has been purified 1,000-fold and its cleavage products have been partially characterized by rotary shadowing electron microscopy. We are further studying the secretion rate of this enzyme by a wide variety of cell types both normal and malignant. A collagenase which preferentially degrades type V collagen has been identified and purified from metastatic tumor cells and endothelial cells migrating toward an angiogenic stimulus. This collagenase has been purified and its cleavage products have been partially characterized by rotary shadowing electron microscopy. The enzyme cuts the type IV procollagen molecule at a single site 25% of the distance from the n-terminal end. We are further studying the secretion rate of this enzyme by a wide variety of cell types both normal and malignant. A collagenase which preferentially degrades type V collagen has been identified and purified from metastatic tumor cells. The type V collagenase has been purified. It has a molecular weight of 80 Kd and cleaves the type V collagen molecule at a single major site near one end. Membrane-associated forms of these enzymes have been discovered. Polyclonal monospecific antibodies and monoclonal antibodies to the type IV collagenase have been prepared. These antibodies react with human breast carcinoma cells in tissue sections.